Thyroid Disorders in the Geriatric

Veterinary Patient
J. Catharine Scott-Moncrieff, MA, MS, Vet MB, MRCVS

KEYWORDS
• Geriatric • Thyroid disorders • Veterinary • Canine • Feline • Hyperthyroidism
• Hypothyroidism

KEY POINTS
• The effects of age, concurrent illness, and administered medications complicate the
diagnosis of thyroid dysfunction in geriatric patients.
• The most common thyroid disorder in dogs is acquired hypothyroidism.
• Tests that are most useful in evaluation in dogs with suspected hypothyroidism are the
total thyroxine concentration (TT4), the free thyroxine concentration, and thyroid-stimulat-
ing hormone concentration.
• The most common thyroid disorder in cats is benign hyperthyroidism. Diagnosis is most
often complicated by the presence of concurrent illness.
• Treatment should be individualized based on individual case characteristics and presence
of concurrent illness.
• Some older cats have a palpable goiter months to years before development of clinical
signs of hyperthyroidism.

INTRODUCTION

Thyroid disorders are an important cause of morbidity in geriatric dogs and cats. The
diagnosis of thyroid dysfunction is more difficult in older animals because of the
impact of age, concurrent illness, and administered medications on serum concen-
trations of thyroid hormone. This article will review the physiology of the thyroid gland
specifically focusing on geriatric patients, discuss the most common causes of
thyroid disease in geriatric patients, and review the special concerns of diagnosis and
treatment in this subset of patients.
THYROID PHYSIOLOGY

Thyroxine (T4) and triiodothyronine (T3) are iodine-containing amino acids synthesized
in the thyroid gland. Thyroid hormones are highly bound to serum proteins with T4

The author has nothing to disclose.

Department Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University,
VCS/LYNN, 625 Harrison Street, West Lafayette, IN 47907-2026, USA
E-mail address: scottmon@purdue.edu

Vet Clin Small Anim 42 (2012) 707–725

http://dx.doi.org/10.1016/j.cvsm.2012.04.012 vetsmall.theclinics.com
0195-5616/12/$ – see front matter © 2012 Elsevier Inc. All rights reserved.
708 Scott-Moncrieff

Hypothalamus

TRH

Pituitary

TSH

rT3

T4 Thyroid glands
Blood
T3

Fig. 1. The hypothalamic-pituitary-thyroid axis. (From Ettinger SJ, Feldman EC. Textbook of
veterinary internal medicine. 7th edition. Philadelphia: Saunders; 2009. p. 1752; with permission.)

more highly bound than T3. In the dog, the thyroid-binding proteins are thyroid hormone-
binding globulin (TBG), transthyretin, albumin, and apolipoproteins, with most T4 bound
to TBG. Thyroid binding globulin is absent in the cat.1 Protein-bound hormones are in
equilibrium with a small fraction of unbound (free) hormone. Only unbound thyroid
hormone enters cells to produce a biologic effect and create a negative feedback effect
on the pituitary and hypothalamus. Tri-iodothyronine enters cells more rapidly, has a
more rapid onset of action, and is 3 to 5 times more potent than T4. Thyroid hormones
bind to receptors in the nuclei; the hormone receptor complex then binds to DNA and
influences the expression of genes coding for regulatory enzymes.
Thyroid hormones have a variety of physiologic effects, which account for the
profound clinical effects of thyroid hormone deficiency on the body. Thyroid hor-
mones increase the metabolic rate and oxygen consumption of most tissues. In the
heart, thyroid hormones have both a positive inotropic and a positive chronotropic
effect, and they increase the number and affinity of beta-adrenergic receptors and
enhance the response to catecholamines. Thyroid hormones have catabolic effects
on muscle and adipose tissue, stimulate erythropoiesis, and regulate both cholesterol
synthesis and degradation.
Thyroid hormone synthesis and secretion are regulated primarily by changes in the
circulating concentration of pituitary thyrotropin (thyroid-stimulating hormone [TSH])
(Fig. 1). Thyroid hormone metabolism by deiodination is regulated by the relative
activity of different deiodinase enzymes and is an important regulatory step in thyroid
hormone metabolism. Outer-ring deiodination of T4 produces T3, whereas inner-ring
deiodination results in formation of biologically inactive reverse T3. T4 and T3 are both
concentrated in the liver and secreted in the bile.

EFFECT OF AGE ON THE HYPOTHALAMIC-PITUITARY-THYROID AXIS

In dogs there is a progressive decline in T4 concentration with age; Serum T4

concentration is highest in puppies and the T4 concentration progressively declines
during adulthood. In a study of 27 female beagles of different ages, mean serum T4
concentrations in old dogs were 40% lower than those of young adult dogs.2 In a
larger study of serum collected from 1074 healthy dogs of differing ages, the mean
TT4 concentration was 21% lower in in dogs older than 6 years compared to young
adult dogs.3 In a longitudinal study of 48 Labrador retrievers studied for 12 years, the
 Geriatric Veterinary Thyroid Disorders 709

Table 1
Mean and median serum TT4 concentration of samples submitted to a reference laboratory
for cats and dogs of different ages
Age, y Mean T4, ␮g/dL Median T4, ␮g/dL No. of Patients
Dogs
0–2 1.94 1.9 1043
3–5 1.91 1.8 2773
6–8 1.83 1.6 6975
9–11 1.75 1.5 5064
12–14 1.67 1.4 4016
⬎14 1.46 1.2 736
All ages 1.78 1.5 20,607
TT4 reference range 1.0–4.0
Cats
0–2 1.93 2.0 414
3–5 2.01 2.1 733
6–8 2.02 2.1 2183
9–11 2.08 2.1 2480
12–14 2.12 2.1 3644
⬎14 2.13 2.1 4477
All ages 2.08 2.1 13931
TT4 reference range 0.8–4.7

Patients with an age listed as 0 were excluded. Samples from cats in which the T4 concentration was
greater than 4.7 ␮g/dL were excluded from the analysis.
Data was provided by IDEXX Laboratories, Inc., Westbrook, ME.

mean TT4 decreased by 29% from the age of 6 to 12 years.4 Similar trends occur for
free T4 (fT4) and TT3 concentrations.3,4 Middle-aged and older dogs also have a
blunted T4 response to TSH compared to young animals.2 Changes in other
parameters of thyroid function have been less studied but increases in anti-T4
antibody in older dogs have been reported.4 Although older dogs as a group have
lower total T4 (TT4) concentrations than younger animals, the mean and median TT4
concentrations still fall within the lower end of most reference ranges (Table 1). None
of the studies cited above reported a range for TT4 in healthy geriatric dogs; it is likely
that for many geriatric dogs a TT4 below the reference range is a normal age-related
change. Reasons for the decline in thyroid hormone concentrations with age in dogs are
not fully understood; proposed reasons include effect of concurrent illness, change in
responsiveness of the thyroid gland to TSH, subclinical thyroid pathology (fibrosis,
atrophy, degenerative changes), and decreased biologic activity of TSH with age.
There are no published studies on how thyroid hormone concentration changes
with age in cats. In a group of more than 13,000 cats of varying ages that had TT4
concentrations within or below the reference range, there was no decline in TT4 with
age (see Table 1).

EFFECT OF CONCURRENT ILLNESS ON HYPOTHALAMIC-PITUITARY-THYROID AXIS

In nonthyroidal illness, total thyroid hormone concentrations tend to decrease, with

the change being more severe with increasing severity of illness. Changes in hormone
710 Scott-Moncrieff

Table 2
Mechanisms by which drugs influence thyroid function in humans
Mechanism Example
Decrease TSH secretion Glucocorticoids
Change thyroid hormone secretion Amiodarone
Decrease gastrointestinal absorption Sucralfate
Alter serum binding Phenylbutazone
Change hepatic metabolism Phenobarbital
Inhibit thyroid peroxidase Sulfonamides

binding to serum carrier proteins (eg, decreased protein concentration, reduced

binding affinity, circulating inhibitors of binding) or peripheral hormone distribution
and metabolism (eg, reduced 5=-deiodinase activity), inhibition of TSH secretion, and
inhibition of thyroid hormone synthesis are proposed to contribute to this change.
Cytokines such as interleukin-1, interleukin-2, interferon gamma, and tumor necrosis
factor alpha decrease TT4 concentrations in dogs.5 The magnitude of decrease
depends on disease severity and is a predictor of mortality.6,7 Thyroid hormone
supplementation does not improve survival in euthyroid humans with decreased
thyroid hormone concentrations or increase survival in euthyroic dogs with conges-
tive heart failure.8 Medical conditions reported to decrease TT4 concentrations in
dogs include hyperadrenocorticism, diabetic ketoacidosis, hypoadrenocorticism,
renal failure, hepatic disease, peripheral neuropathy, generalized megaesophagus,
heart failure, neoplasia, critical illness or infection, and surgery or anesthesia.9 –15

EFFECT OF DRUGS ON THE HYPOTHALAMIC-PITUITARY-THYROID AXIS

Many drugs influence the thyroid gland by a variety of mechanisms (Table 2). The
effect of comonly used drugs on thyroid function in dogs is shown in Table 3.16 –22
Glucocorticoids influence peripheral metabolism of thyroid hormones and inhibit TSH
secretion. The effect of glucocorticoids depends on the dose and specific prepara-
tion. Oral administration of glucocorticoids at immunosuppressive doses causes
rapid decreases in TT4, fT4, and T3 but little change in serum TSH. Thyroid hormone
concentrations return to normal within 1 week after stopping treatment if dosing is for
3 weeks or less. Longer treatment may prolong duration of suppression. Sulfon-
amides block iodination of thyroglobulin and in dogs can cause clinical hypothy-
roidism in a dose- and duration-dependent manner. Effects are reversible within 2
to 4 weeks of discontinuation of therapy. Phenobarbital administration in dogs
causes decreased TT4 and fT4 concentrations and mild increases in TSH concen-
tration without clinical evidence of hypothyroidism. The effect of drugs other than
methimazole on thyroid hormone concentrations in cats has received little
attention.

EFFECT OF BREED ON THE HYPOTHALAMIC-PITUITARY-THYROID AXIS

Most laboratories report reference ranges based on measurement of thyroid hormone

concentrations in groups of dogs of various breeds and ages; however, there are
significant differences between breeds in regard to thyroid hormone concentration. In
a study of young healthy greyhounds, 91% of the dogs had a TT4 concentration below
the non– breed-specific reference range and 16% had TT4 concentrations that were
either at or below the limit of detection of the assay.23 fT4 was lower than the
 Geriatric Veterinary Thyroid Disorders 711

Table 3
Drugs that have been demonstrated to influence thyroid function in dogs
TT4 fT4 TSH Clinical Signs of
Drug (2 or N) (2 or N) (1 or N) Hypothyroidism? Notes
Glucocorticoids 2 (2 or N) N No Effect dose and
duration dependent
Phenobarbital 2 2 Slight 1 No TSH not increased
outside reference
range
Trimethoprim/ 2 2 1 Yes Effect dose and
sulfonamides duration dependent
Non-steroidal Effect varies
antiinflammatory depending on
drugs specific drug used
Aspirin 2 N N No
Deracoxib N N N No
Ketoprofen N N N No
Meloxicam N N N No
Carprofen N N N No
Tricyclic Effect of other tricyclic
antidepressant antidepressants
unknown in dog
Clomipramine 2 2 N No
Propanolol N N N No
Potassium bromide N N N No

Abbreviation: N, no change.

non– breed-specific reference range in 21% of dogs and at or below the limit of
detection in 13% of dogs. In the same study, T3 concentrations were all within the
non– breed-specific reference range. The reason for the difference in thyroid hormone
concentrations between greyhounds and other breeds has not yet been elucidated,
but studies suggest that it is not due to changes in concentration or function of thyroid
binding globulin.24 There are no published studies investigating the change in
concentration of TT4 or fT4 with aging in greyhounds; however, in salukis and
sloughis, TT4 and fT4 concentrations decline with age as has been reported in
non–sight hound breeds.25,26 Other breeds in which breed-specific changes in
thyroid hormone parameters have been reported are given in Table 4.23-31

CANINE THYROID DYSFUNCTION

The most common thyroid disorders of geriatric dogs are acquired hypothyroidism
and thyroid neoplasia.

Canine Hypothyroidism
Pathogenesis
Hypothyroidism results from decreased production of T4 and T3 from the thyroid
gland. Acquired primary hypothyroidism is caused by lymphocytic thyroiditis or
idiopathic thyroid atrophy. Canine thyroiditis is believed to be the cause of hypothy-
roidism in approximately 50% of hypothyroid dogs.32 Lymphocytic thyroiditis has
712 Scott-Moncrieff

Table 4
Canine breeds with unique thyroid hormone reference ranges
TT4 fT4 TT3 TSH
Breed (2 or N) (2 or N) (2 or N) (1 or N)
Greyhound 2 2 Variable N
Whippet 2 N — N
Saluki 2 2 2 1
Sloughi 2 2 or 1 (ED) — 1
Conditioned Alaskan sled dogs 2 2 2 Variable

Abbreviations: ED, equilibrium dialysis; N, no change.

been identified as a risk factor for thyroid neoplasia.33 Secondary hypothyroidism

(deficiency of TSH) is regarded as rare in dogs.

Epidemiology
Hypothyroidism is typically a disease of middle-aged to older dogs. Golden retrievers
and Doberman pinschers are among the breeds reported to be at higher risk for
hypothyroidism while many breeds have been reported to be at higher risk of
thyroiditis (Table 5). The peak prevalence of detection of anti-thyroglobulin antibodies
is 2 to 4 years of age, which fits with the hypothesis that thyroiditis may progress to
complete thyroid failure over time.32 The severity and progression of thyroiditis seem
to be dependent on breed, with some breeds having relatively rapid progression to
thyroid failure while other breeds such as the beagle progress to thyroid failure much
more slowly, if at all.32 Studies do not suggest a consistent association of hypothy-
roidism with sex or neuter status.

Clinical signs
Common clinical signs include lethargy, mental dullness, weight gain, sluggishness,
and cold intolerance. Dermatologic changes such as dry scaly skin, changes in
haircoat quality or color, alopecia, seborrhea, and superficial pyoderma occur in 60%
to 80% of hypothyroid dogs. Alopecia is usually bilaterally symmetric and is first
evident in areas of wear, such as the lateral trunk, ventral thorax, and tail. The head
and extremities tend to be spared. The hair may be brittle and easily epilated, and loss
of undercoat or primary guard hairs may result in a coarse appearance or a puppy-like
haircoat. Fading of coat color may also occur, and failure of hair regrowth after
clipping is common. Other dermatologic changes in hypothyroid dogs include
hyperkeratosis, hyperpigmentation, comedone formation, hypertrichosis, ceruminous
otitis, poor wound healing, increased bruising, and myxedema.
Neurologic clinical signs are rare but important manifestations of hypothyroidism.
Neurologic signs include peripheral neuropathy, cranial nerve dysfunction (facial,
trigeminal, vestibulocochlear), and cerebral dysfunction (seizures, disorientation,
circling). Cardiovascular abnormalities in hypothyroid dogs include sinus bradycardia,
weak apex beat, low QRS voltages, and reduced left ventricular pump function.

Diagnosis
Diagnostic testing for hypothyroidism should only be pursued if there is clinical
evidence of thyroid disease based on evaluation of the history and physical exami-
nation. Routine screening of asymptomatic dogs for hypothyroidism will increase the
 Geriatric Veterinary Thyroid Disorders 713

Table 5
Twenty breeds with the highest and 20 breeds with the lowest prevalence of
thyroglobulin antibody in 140,821 serum samples submitted for investigation of thyroid
disease
Name Total Sera TgAA Positive Prevalence
English setter 585 184 31%
Old English sheepdog 368 86 23%
Boxer 2642 496 19%
Giant schnauzer 263 49 19%
American pit bull terrier 345 64 19%
Beagle 2452 449 18%
Dalmatian 1372 246 18%
German wirehaired pointer 112 20 18%
Maltese dog 594 105 18%
Rhodesian ridgeback 626 107 17%
Siberian husky 483 80 17%
American Staffordshire terrier 151 24 16%
Cocker spaniel 8576 1305 15%
Chesapeake Bay retriever 509 74 15%
Tibetan terrier 106 15 14%
Shetland sheepdog 5765 813 14%
Golden retriever 17,782 2397 13%
Borzoi 266 35 13%
Husky 646 84 13%
Brittany 556 71 13%
Dachshund 3612 115 3%
Basset hound 699 22 3%
Cairn terrier 590 18 3%
Schnauzer, unspec. 1257 38 3%
Wirehaired fox terrier 170 5 3%
Cavalier King Charles spaniel 274 8 3%
Welsh corgi, undet. 457 13 3%
Yorkshire terrier 1178 33 3%
Norwegian elkhound 263 7 3%
Belgian Tervuren 235 6 3%
Chihuahua 611 15 2%
Greyhound 1409 32 2%
Pekingese 407 9 2%
Boston terrier 500 11 2%
Pomeranian 1301 26 2%
Irish wolfhound 210 4 2%
Whippet 114 2 2%
Soft-coated Wheaten terrier 214 3 1%
Bichon frise 657 8 1%
Miniature Schnauzer 828 10 1%

Overall TgAA prevalence in this study was 10%.

Abbreviations: TgAA, thyroglobulin antibody; undet., undetermined; unspec., unspecified.
From Graham PA, Refsal KR, Nachreiner RF. Etiopathologic findings of canine hypothyroidism.
Vet Clin N Am Small Anim Pract 2007;37(4):617–31; with permission.
714 Scott-Moncrieff

Table 6
Sensitivity, sensitivity, and accuracy of 4 assays for fT4 in dogs and cats
Cats Dogs

Sensitivity, Specificity, Accuracy, Sensitivity, Specificity, Accuracy,

Assay % % % % % %
Analog fT4 87 100 89 80 97 89
MED IVD 87 100 89 92 90 91
MED AN 92 67 89 71 100 86
Two-step Diasorin 89 100 91 96 90 93

The dog population included 56 dogs with clinical signs of hypothyroidism (31 euthyroid, 25
hypothyroid). The cat population included 45 cats with clinical signs of hyperthyroidism (6 euthy-
roid, 39 hyperthyroid). Assays included the Immulite 2000 Veterinary fT4 (Siemens Healthcare
Diagnostics Products Ltd., Llanberis, Gwynedd, UK), Direct free T4 by dialysis (MED IVD; IVD
Technologies, Santa Ana, CA, USA), fT4 by equilibrium dialysis (MED AN; Antech Diagnostics,
Irvine, CA, USA), and the Gammacoat fT4 (2-step) Radioimmunoassay (Diasorin, Stillwater, MN,
USA).

likelihood of a false-positive result, especially in the geriatric population. Measure-

ment of TT4 concentration is a sensitive initial screening test for hypothyroidism.
Tests to confirm the diagnosis include measurement of fT4 and thyrotropin (TSH)
concentration and provocative thyroid function tests. Evidence of thyroiditis increases
suspicion for thyroid dysfunction. Evaluation of response to thyroid hormone supple-
mentation may be necessary to confirm the diagnosis. Clinicopathologic changes that
are commonly present in dogs with hypothyroidism such nonregenerative anemia,
fasting hypertriglyceridemia, and hypercholesterolemia increase the index of suspi-
cion for hypothyroidism.

TT4 concentration Measurement of a TT4 concentration well within the reference range
indicates normal thyroid function; however, a TT4 concentration below the normal
range may be caused by other factors such as nonthyroidal illness, drug administra-
tion, age, and breed variation.

fT4 concentration Because only the unbound fraction of serum T4 is biologically active,
measurement of fT4 should be more sensitive and specific for the diagnosis of hypothy-
roidism than TT4. There are a number of different assays currently used in dogs for
measurement of fT4 and their diagnostic performance varies (Table 6).34 Although
measurement of fT4 concentration is believed to be slightly more specific and sensitive for
diagnosis of canine hypothyroidism than measurement of TT4, concurrent illness, drug
administration, and breed variability may still suppress fT4 concentration.

Total T3 concentration (TT3) Measurement of TT3 is not recommended for routine

diagnosis of canine hypothyroidism because T3 concentration frequently fluctuates
out of the reference range in euthyroid dogs.

Thyrotropin concentration (TSH) Measurement of canine TSH concentration is helpful

to confirm the diagnosis of hypothyroidism in dogs with a low TT4 concentration,
because low TT4 in conjunction with high TSH is highly specific for diagnosis of
hypothyroidism (Table 7).35–37 The limitation of measurement of TSH is the lack of
 Geriatric Veterinary Thyroid Disorders 715

Table 7
Performance of various diagnostic tests for hypothyroidism in dogs
Test Sensitivity, % Specificity, % Accuracy, %
TT4 89–100 75–82 85
fT4 80–98 93–94 95
TSH 63–87 82–93 80–84
TSH/T4a 63–67 98–100 82–88
TSH/fT4a 74 98 86
a
A dog was considered to have hypothyroidism only if the T4 or fT4 was low and the TSH was high.
The data are compiled from 3 published studies of a total of 100 hypothyroid dogs and 164
euthyroid dogs. Not all studies evaluated all diagnostic tests listed.
Data from Refs.34 –36

assay sensitivity; approximately 30% of hypothyroid dogs have a TSH concentration

within the reference range.

TSH stimulation test The TSH stimulation test is a test of thyroid reserve. It is
considered the gold standard test for assessment of thyroid function in dogs, but its
use is limited by the expense of TSH. The protocol requires collection of a serum
sample for measurement of T4, administration of 75 to 150 ␮g/dog IV of human
recombinant TSH with an additional blood sample for TT4 collected after 6 hours. The
higher dose is recommended in dogs with concurrent disease and those receiving
medication.38 Hypothyroidism is confirmed by a pre and post TT4 concentration below
the reference range for basal TT4 concentration. Euthyroidism is confirmed by a post TT4
concentration greater than 2.5 ␮g/dL. Interpretation of intermediate results should take
into consideration the clinical signs and severity of concurrent systemic disease.

Diagnostic imaging Ultrasonography may be useful in evaluation of dogs with

suspected hypothyroidism. The thyroid gland in many hypothyroid dogs has a smaller
volume and cross-sectional area compared to euthyroid dogs and tends to be less
echogenic. Nuclear scintigraphy also has high discrimination for evaluation of dogs
with suspected hypothyroidism; however, it is rarely performed in clnincal practice.39

Therapeutic trial Response to therapy is sometimes the most practical approach to

confirming a diagnosis of hypothyroidism. After ruling out nonthyroidal illness,
supplementation with synthetic sodium L-thyroxine (L-T4) should be initiated at a
dosage of 0.02 mg/kg q 12 hours. If improvement is noted, therapy should be
temporarily withdrawn. Recurrence of clinical signs is consistent with a diagnosis of
hypothyroidism. If clinical signs do not recur, thyroid responsive disease in which
clinical signs improve due to the nonspecific effects of thyroid hormone should be
suspected. If there is no response to treatment after 2 to 3 months of appropriate
therapy, and 4- to 6-hour post-pill serum TT4 concentrations are within the appro-
priate therapeutic range, therapy should be withdrawn and other diagnoses pursued.

Diagnosis of thyroiditis
Dogs with thyroiditis may have serum antibodies directed against thyroglobulin, T3, or
T4. Anti-thyroglobulin antibodies are present in 36% to 50% of hypothyroid dogs.40
Anti-T3 antibodies are detected in 34% of hypothyroid dogs, while anti-T4 antibodies
are found in 15% of hypothyroid dogs.41 Because dogs with thyroiditis may still have
716 Scott-Moncrieff

adequate thyroid reserve, positive antibody titers are not diagnostic of hypothyroid-
ism; however, a positive titer increases the likelihood of thyroid dysfunction in dogs
with equivocal thyroid hormone/TSH concentrations.

Treatment
The treatment of choice for hypothyroidism, regardless of the underlying cause, is
42
L-T4. Administration of L-T4 with food may decrease bioavailability. Treatment with
synthetic T3 is not recommended because it has a shorter half-life, requires admin-
istration 3 times daily, and is more likely to cause iatrogenic hyperthyroidism.
Treatment with T3 may be indicated if there is inadequate gastrointestinal absorption
of L-T4 because T3 is better absorbed in the gastrointestinal tract. The use of
desiccated thyroid extract, thyroglobulin, or “natural” thyroid preparations is not
recommended because the bioavailability and T4:T3 ratio of these compounds are
variable, making consistent dosing difficult.
Twice-daily administration of T4 at a dosage of 0.02 mg/kg q 12 hours is
recommended initially. If clinical signs resolve and T4 concentrations are within the
therapeutic range after 4 to 8 weeks of therapy, the frequency of T4 administration can
be decreased to once daily. Because of Individual variability in T4 absorption and
serum half-life, the dose should be adjusted based on the measured serum T4
concentration 4 to 6 hours after dosing. Therapeutic monitoring also minimizes the
effect of any differences in potency and bioavailability between different brands of
L-thyroxine. For otherwise healthy adult dogs, TT4 concentration should be at the high
end or slightly above the reference range 4 to 6 hours after dosing; however, therapy
should be individualized based on clinical response, presence of concurrent illness,
age, and concurrent drug administration. Improvement in activity should be evident
within the first 1 to 2 weeks of treatment; weight loss should be evident within 8
weeks. Achievement of a normal hair coat may take several months and the coat may
initially appear worse as telogen hairs are shed. Neurologic deficits improve rapidly
after treatment but complete resolution may take 8 to 12 weeks.

Treatment in presence of concurrent illness Concurrent illness is common in the

geriatric population. The appropriate therapeutic range for hypothyroid dogs with
concurrent nonthyroidal illness or that are being treated with drugs such as pheno-
barbital is unknown but is likely lower than the range for healthy dogs. Concurrent
measurement of serum TSH concentration may be helpful in interpretation of the
post-pill TT4 concentration. A TSH concentration that persists above the reference
range suggests inadequate supplementation or poor owner compliance; conversely,
if the TSH is suppresssed and clinical signs have resolved, it is not necessary to
increase the L-T4 dose to drive the post-pill T4 concentration into the therapeutic
range, especially in geriatric patients. Unfortunately, current assays for TSH are not
sensitive enough to identify dogs that are oversupplemented with L-T4 .
Caution should be used when initiating treatment with thyroid hormone in certain
disease states. Thyroid hormone supplementation increases myocardial oxygen
demand and may cause cardiac decompensation in dogs with underlying heart
disease. For this reason, the initial dose of L-T4 should be 25% to 50% of the usual
starting dose. The dose may then be increased incrementally based on the results of
therapeutic monitoring and reevaluation of cardiac function. In dogs with concurrent
hypoadrenocorticism, replacement of mineralocorticoid and glucocorticoid defi-
ciency should be initiated before treatment with L-T4, because increased basal
metabolic rate after supplementation may exacerbate electrolyte disturbances.
 Geriatric Veterinary Thyroid Disorders 717

Treatment failure Incorrect diagnosis of hypothyroidism is the most common reason

for treatment failure. Diseases such as hyperadrenocorticism, atopy, and flea hyper-
sensitivity may have clinical signs similar to those of hypothyroidism and may be
associated with decreased thyroid hormone concentrations. Many other disorders
result in physiologically appropriate decreases in thyroid hormone concentrations.
Other less common reasons for a poor response to treatment include poor absorption
of T4 from the gastrointestinal tract or problems with owner compliance. These
situations can be identified by therapeutic monitoring.

Canine Thyroid Neoplasia

Canine thyroid tumors are the most common endocrine tumors in dogs and comprise
1.1% of all canine neoplasms.43 Breeds at increased risk include the beagle, golden
retriever, and Siberian husky, and there is no sex predisposition. The risk of thyroid
cancer is highest in dogs between 10 and 15 years of age. Clinically significant canine
thyroid tumors are usually large, nonfunctional, unilateral, invasive, and malignant,
and most are follicular carcinomas or adenocarcinomas, with only 9% being adeno-
mas.43 Neoplasms metastatic to the thyroid gland are rare. Hypothyroidism is
reported in 18% to 35% of malignant thyroid tumors, while 5% to 20% of canine
thyroid carcinomas cause hyperthyroidism. Canine thyroid carcinoma is character-
ized by local tissue invasion and a high rate of metastasis, particularly to the lungs,
retropharyngeal lymph nodes, and the liver.

Clinical signs
Clinical signs are most commonly due to a space occupying cervical mass. Affected
dogs may exhibit dyspnea, coughing, dysphagia, retching, anorexia, facial edema,
and dysphonia. Other clinical signs include vomiting, listlessness, and weight loss. In
dogs with functional thyroid tumors, polyuria and polydipsia, restless behavior,
polyphagia, weight loss, diarrhea, and tachycardia may be observed. Signs of
hypothyroidism may be present if there is complete bilateral thyroid destruction.
Physical examination findings include a firm, usually asymmetric mass in the cervical
region and often submandibular lymphadenopathy. Dyspnea, cachexia, and neck
pain occur less commonly. Cardiac arrhythmias or murmurs may be detected in
hyperthyroid dogs.

Diagnosis
Mild nonregenerative anemia, leukocytosis, mild azotemia, and increased serum liver
enzyme activities are typical findings on the minimum database. Hypercalcemia may
occur due to concurrent primary hyperparathyroidism or as a paraneoplastic syn-
drome. Thoracic and abdominal radiographs and abdominal ultrasound may identify
heart-based, pulmonary, hepatic, or visceral metastases. Up to 60% of dogs with
thyroid carcinoma have radiographic evidence of pulmonary metastasis at the time of
diagnosis. Cervical ultrasound and computed tomography may be useful in deter-
mining the extent of tumor invasion. Thyroid testing is indicated to determine thyroid
status. Increased serum thyroid hormone concentrations due to the presence of
autoantibodies to T3 or T4, are an important differential for increased serum TT4
concentration.
Sodium pertechnetate is the isotope of choice for imaging of thyroid tumors.44
Dogs with nonfunctional thyroid carcinomas tend to have poorly circumscribed
heterogeneous isotope uptake. Dogs with functional carcinomas usually have in-
tense, well-circumscribed, homogeneous uptake of isotope. Fine-needle aspiration
cytology is useful to differentiate thyroid tumors from abscesses, cysts, mucoceles,
718 Scott-Moncrieff

and lymph node; however, cytology is not helpful in definitively differentiating benign
from malignant thyroid neoplasia. Aspirates may be nondiagnostic due to peripheral
blood contamination. Use of larger biopsy instruments, such as a large-bore needle
or biopsy needle, is not recommended because most thyroid tumors are highly
vascular. A surgical biopsy is necessary for differentiation between a thyroid adenoma
and carcinoma. If the mass is clearly not amenable to complete surgical excision, an
incisional wedge biopsy should be obtained.

Treatment
Surgical resection is the initial treatment of choice for dogs with thyroid tumors,
regardless of the functional status of the tumor.45 Thyroid tumors that are mobile and
well circumscribed are the best surgical candidates. Even if complete removal of the
tumor is not possible, surgery provides tissue samples for histopathology and may
also alleviate some of the clinical signs associated with the tumor. Surgical risks relate
to the high vascularity of thyroid tumors and the risk of damage to the recurrent
laryngeal nerves, parathyroid glands, and major blood vessels. In dogs with extensive
local tumor infiltration or with distant metastases, surgical resection is strictly
palliative. Radiation therapy, radioiodine therapy, or adjunctive chemotherapy should
be considered in these patients.
External beam radiation therapy is effective for local control of thyroid tumors but
is ineffective in prevention of metastatic disease.46 Treatment with 131I is a viable
alternative to external beam irradiation in tumors that concentrate iodine.47,48 Canine
thyroid carcinoma has a guarded prognosis due to the propensity for both local tissue
invasion and metastasis to distant sites. Chemotherapy alone is unlikely to result in
total remission of thyroid carcinoma. Doxorubicin, cisplatin, and combination therapy
utilizing doxorubicin, cyclophosphamide, and vincristine have been used empirically
to treat thyroid carcinoma in the dog.

FELINE THYROID DYSFUNCTION

The most common thyroid disorder of geriatric cats is hyperthyroidism due to thyroid
adenoma or hyperplasia. Hyperthyroidism due to thyroid carcinoma occurs in less
than 2% of hyperthyroid cats, while nonfunctional thyroid neoplasia is extremely rare.
Spontaneous hypothyroidism is extremely rare in cats but hypothyroidism may occur
following treatment of hyperthyroidism.

Feline Hyperthyroidism
Feline hyperthyroidism is the most common endocrine disease of geriatric cats with
a reported hospital prevalence of 3%.49 The clinical syndrome is due to autonomous
secretion of thyroid hormones by the thyroid gland. Histopathology of affected
thyroids usually reveals thyroid adenomatous hyperplasia or benign thyroid adenoma.
Pathologic changes may affect one or both lobes of the thyroid gland and in 70% of
cats the changes are bilateral. Ectopic hyperplastic thyroid tissue is present in up to
20% of cats.

Pathogenesis
Case-control studies have identified risk factors for hyperthyroidism in cats including
age, breed (pure bred cats are at decreased risk), use of cat litter (may be a surrogate
for indoor lifestyle), and consumption of an increased proportion of canned cat food
in the diet. It is currently believed that the cause is multifactorial with numerous
nutritional and environmental risk factors such as ingestion of goitrogenic compounds
like phalates and bisphenol, high intake of dietary soy, and decreased or increased
 Geriatric Veterinary Thyroid Disorders 719

intake of dietary iodine potentially playing a role.50 The cumulative effects of these
exposures over many years may lead to mutations in thyroid follicular cells that
ultimately result in autonomous thyroid hormone secretion. Mutations that have been
identified in thyroid tissue from hyperthyroid cats include TSH receptor gene and G
protein mutations.50

Epidemiology
Feline hyperthyroidism is a disease of geriatric cats with a mean age of 13 years. The
range of age is 6 to 25 years of age, so occasionally the diagnosis is made in a young
or middle-aged cat.51 Most studies have shown no sex or breed predisposition,
although pure bred cats are underrepresented and female cats may be at increased
risk.49

Clinical signs
Clinical signs include weight loss, diarrhea, chronic vomiting, polyphagia, polyuria,
polydipsia, muscle weakness, poor hair coat, and hyperactivity. Anorexia and lethargy
are reported in some patients. Additional findings on physical examination include
tachycardia, heart murmur, tachypnea, cardiac arrhythmias, dehydration, and a
palpable thyroid nodule. Other disorders common in older cats such as renal failure,
congestive heart failure, gastrointestinal disease, and diabetes mellitus may mimic
some of the clinical signs of hyperthyroidism.

Diagnosis
Since hyperthyroidism is a geriatric disease, it is important to investigate for the
presence of concurrent disease and to take into account the special needs of geriatric
patients when planning therapy. The minimum database should include a detailed
history and physical examination, serum TT4 concentration, complete blood count,
biochemical profile, thoracic radiographs, and arterial blood pressure. Other diagnos-
tic tests indicated in some patients include cardiac ultrasound, abdominal ultrasound,
ophthalmologic examination, and electrocardiogram. A technetium scan is recom-
mended in hyperthyroid cats undergoing surgical thyroidectomy.
Polycythemia or a stress leukogram may be present on the complete blood count.
A biochemical panel usually reveals mild to moderate increases in alanine amino-
transferase, aspartate aminotransferase, and alkaline phosphatase. As much as 80%
of the increased alkaline phosphatase is due to the bone isoenzyme of alkaline
phosphatase.52 Other common findings include azotemia, hyperphosphatemia, hy-
pokalemia, and increased fasting ammonia concentration.53 Approximately 10% of
cats are azotemic at time of diagnosis and 50% have increased protein:creatinine
ratio.51 Thoracic radiographs may reveal cardiomegaly, pleural effusion, pulmonary
edema, pericardial effusion, or concurrent diseases such primary or metastatic
neoplasia. Echocardiography usually shows abnormalities consistent with mild hy-
pertrophic cardiomyopathy; however, more severe heart disease is sometimes
present. The most common abnormalities on electrocardiogram are sinus tachycardia
and increased amplitude of the R wave (lead II). Hypertension is diagnosed in
approximately 15% of cats and is significantly correlated with decreased survival
time.51

TT4 concentration Diagnosis of hyperthyroidism can usually be confirmed by mea-

surement of a single serum TT4 concentration. In cats with early hyperthyroidism or
with concurrent nonthyroidal illness, the TT4 concentration may be within the upper
half of the reference range. If the TT4 is high normal or borderline, the measurement
720 Scott-Moncrieff

should be repeated after concurrent diseases have been treated and resolved, or after
a period of 4 to 8 weeks, because hyperthyroidism is a chronic progressive disease
and serum TT4 concentrations increase over time. In cases in which a immediate
diagnosis is necessary, a fT4 concentration, T3 suppression test, or nuclear scintig-
raphy should be considered.

fT4 concentration Measurement of fT4 concentration is slightly more sensitive than the
TT4 concentration for diagnosis of hyperthyroidism; however, some euthyroid cats
with concurrent illness have false-positive increases in fT4 concentration, with
resultant poor specificity (Table 6).54 Thus, the fT4 concentration should only be
interpreted in the context of the TT4 concentration. If the TT4 is at the high end of the
reference range and the freeT4 is high, a diagnosis of hyperthyroidism can be
confirmed. Most cats with a low T4 concentration and a high fT4 concentration are not
hyperthyroid. If there is strong clinical suspicion of hyperthyroidism, further diagnostic
testing such as the T3 suppression test or technetium scan should be considered.

T3 suppression test Baseline T3 and T4 concentrations are measured and then

synthetic liothyronine (T3) is administered at a dose of 25 ␮g/cat orally q 8 hours for
7 treatments. T3 and T4 concentrations are then measured again 2 to 6 hours after the
last treatment. In euthyroid cats, the second T4 concentration should be less than 1.5
␮g/dL or more than 50% lower than the baseline T4 concentration.55 Cats with
hyperthyroidism fail to suppress. T3 concentrations are measured before and after T3
administration to confirm good client compliance and adequate absorption of the
drug.

Technetium scan In cats with suspected hyperthyroidism that have severe concurrent
illness, a radioisotope scan using sodium pertechnetate is the most reliable diagnos-
tic test for confirmation of hyperthyroidism.55 As many as 20% of hyperthyroid cats
have ectopic thyroid tissue on scintigraphy.56

Treatment
Treatment options for feline hyperthyroidism include oral antithyroid therapy, radio-
active iodine therapy, surgical thyroidectomy, and dietary iodine restriction. The
choice of treatment depends on the presence of other disease states, the age of the
cat, the cat’s tolerance for hospitalization, tolerance of antithyroid medications, owner
preference, and the results of other diagnostic tests (eg, cardiac evaluation, techne-
tium scan).

Antithyroid drugs (thiourylenes) Methimazole is the most common antithyroid drug

used in cats in North America. Carbimazole is a prodrug of methimazole that is the
most frequently used antithyroid drug in Europe. Treatment with methimazole is
indicated in cats with concurrent medical problems, for test therapy in patients with
suspected renal dysfunction, and in cases with financial limitations. Methimazole
should be initiated at an initial dose of 2.5 mg po q 8 to 12 hours and then titrated to
effect. The final dose required ranges from 2.5 to 20 mg/d, and most cats respond
within 2 to 3 weeks of starting therapy. The most common adverse effects seen in
20% of cats are anorexia, vomiting, and lethargy. Transdermal administration of
methimazole is associated with a lower risk of gastrointestinal side effects.57 Mild
hematologic abnormalities such as leukopenia, lymphocytosis, and eosinophilia are
relatively common. More severe hematologic abnormalities such as severe neutro-
penia and thrombocytopenia occur in a small percentage of cats. Rarely, excoriation
 Geriatric Veterinary Thyroid Disorders 721

of the head and neck, toxic hepatopathy, and bleeding diatheses may occur.
Monitoring recommendations for cats treated with methimazole include a complete
blood count, platelet count, biochemical profile, and TT4 concentration every 2 weeks
for the first 3 months of therapy. The timing of sample collection for evaluation of TT4
concentration in relation to time of administration of medication does not appear to be
important in assessing response to methimazole.58 The advantages of antithyroid
drugs include low cost and reversibility of the antithyroid effect. Disadvantages
include the risk of adverse effects, failure to respond in some patients, poor owner
compliance, and control rather than cure of disease. Methimazole is commonly used
to evaluate the effect of treatment upon renal function because treatment of
hyperthyroidism may unmask underlying renal disease. If indicators of renal function
remain stable during treatment with methimazole, it is more likely that definitive
therapy will be well tolerated. If clinical signs of renal failure develop or there is a
significant worsening of azotemia after establishing euthyroidism, definitive therapy
with 131I or thyroidectomy should be avoided and consideration should be given to
long-term medical management.

Radioactive iodine 131I is the radionuclide of choice for the treatment of hyperthy-
roidism. The isotope has a half-life of 8 days and is a beta and gamma emitter. 131I is
administered intravenously or subcutaneously at either a fixed dose (usually 4 – 6 mCi)
or a calculated dose based on the weight of the cat, the size of the thyroid gland, and
the T4 concentration. It is usually recommended that antithyroid drugs are discontin-
ued 7 to 14 days prior to treatment; however, current evidence does not support this
recommendation.59 After injection, 131I is taken up by thyroid follicular cells and
concentrated in the colloid. Emission of ␤ particles destroys functional thyroid tissue
without causing damage to normal tissues such as the parathyroid glands. Normal
thyroid tissue is spared because it is atrophic and does not concentrate iodine.
Thyroid hormone concentrations decline in 5 to 10 days, and clinical improvement is
usually observed within 2 weeks, although in some cats the response may be
delayed. Treatment with 131I is safe and does not require anesthesia; there is no risk
of iatrogenic hypoparathyroidism; and thyroid tissue or metastatic thyroid carcinoma
can be effectively treated. In cats with thyroid carcinoma, doses of 20 to 30 mCi are
used. Disadvantages of 131I are expense, lack of histopathologic evaluation of thyroid
tissue, and requirement for isolation for several days after treatment. Radioactive
iodine is the treatment of choice for most hyperthyroid cats; however, it should be
avoided in patients with other serious medical problems that require therapy during
isolation, in cats with renal failure that worsens after treatment with antithyroid drugs,
and in patients that do not tolerate hospitalization.

Thyroidectomy Surgical thyroidectomy is less commonly performed for treatment of

hyperthyroid cats because of the increasing availability of radioactive iodine treat-
ment. Disadvantages include the need for general anesthesia, the risk of iatrogenic
hypoparathyroidism or hypothyroidism after bilateral thyroidectomy, potential for
ectopic thyroid tissue,56 and morbidity associated with the surgical procedure. The
advantages include rapid response to treatment, short hospital stay, convenience in
the private practice setting, and the opportunity histopathologic evaluation of thyroid
tissue. Indications for thyroidectomy are cats with suspected thyroid carcinoma and
cats with unilateral thyroid disease confirmed by nuclear scintigraphy.

Iodine restriction Dietary iodine restriction to less than 0.32 parts per million reduces
the circulating thyroid hormone concentrations into the normal range in hyperthyroid
722 Scott-Moncrieff

cats and has potential as a long-term management strategy.60 Long-term outcome in

cats managed by dietary iodine restriction alone has yet to be determined.

Prognosis
Retrospective studies suggest that age, proteinuria, and hypertension are associated
with decreased survival times in treated hyperthyroid cats.51 Cats treated with
methimazole alone had a shorter median survival time than cats treated with
radioactive iodine alone or methimazole followed by radioactive iodine.61
Iatrogenic hypothyroidism contributes to azotemia after treatment of hyperthyroid
cats and is associated with reduced survival times.

Hypothyroidism
Hypothyroidism may occur after bilateral thyroidectomy or radioactive iodine therapy.
Clinical signs include anorexia, lethargy, weight gain, poor hair coat, and alopecia. In
most cases, hypothyroidism is transient and resolves within weeks of treatment, but
persistent hypothyroidism 6 months after treatment contributes to azotemia and is
associated with reduced survival time.63

Nonfunctional thyroid nodules

In older cats, it is not uncommon to palpate an enlarged thyroid gland in an apparently
healthy cat. Possible differential diagnoses include early hyperthyroidism in which a
goiter is present but the thyroid gland is not fully autonomous, thyroid cyst, thyroid
cystadenoma, or nonfunctional thyroid adenoma or carcinoma.62,63 Nonfunctional
thyroid carcinoma is rare in the cat. If an obvious cervical nodule is palpated in a cat
with a normal T4 concentration, a fine needle aspirate should be considered to
determine the tissue of origin. Unfortunately, the accuracy of thyroid cytology for
differentiation of benign from malignant thyroid disease is poor.

SUMMARY

The effects of age, concurrent illness, and administered medications complicate the
diagnosis of thyroid dysfunction in geriatric patients. Interpretation of thyroid hor-
mone testing should take these factors into account. The most common thyroid
disorder in dogs is acquired hypothyroidism. Tests that are most useful in evaluation
in dogs with suspected hypothyroidism are TT4, fT4, and TSH concentration.
Therapeutic monitoring should be utilized for monitoring treatment of canine hypo-
thyroidism. The therapeutic range for TT4 in geriatric dogs with concurrent illness is
likely to be lower than that for younger healthy adult dogs. The most common thyroid
disorder in cats is benign hyperthyroidism. Diagnosis is most often complicated by
the presence of concurrent illness. Treatment should be individualized based on
individual case characteristics and presence of concurrent illness. Some older cats
have a palpable goiter months to years before development of clinical signs of
hyperthyroidism.

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